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Do common genetic variants in endotoxin signaling pathway contribute to predisposition to alcoholic liver cirrhosis?
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Jan Petrášek
Veröffentlicht/Copyright:
12. März 2009
Abstract
Background: Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), produced by endotoxin-activated Kupffer cells, play a key role in the pathogenesis of alcoholic liver cirrhosis (ALC). Alleles TNFA –238A, IL1B –31T and variant IL1RN*2 of repeat polymorphism in the gene encoding the IL-1 receptor antagonist increase production of TNF-α and IL-1β, respectively. Alleles CD14 –159T, TLR4 c.896G and TLR4 c.1196T modify activation of Kupffer cells by endotoxin. We confirmed the published associations between these common variants and genetic predisposition to ALC by means of a large case-control association study conducted on two Central European populations.
Methods: The study population comprised a Czech sample of 198 ALC patients and 370 controls (MONICA project), and a German sample of 173 ALC patients and 331 controls (KORA-Augsburg), and 109 heavy drinkers without liver disease.
Results: Single locus analysis revealed no significant difference between patients and controls in all tested loci. Diplotype [IL1RN*2/*2; IL1B –31T+] was associated with increased risk of ALC in the pilot study, but not in the validation samples.
Conclusions: Although cytokine mediated immune reactions play a role in the pathogenesis of ALC, hereditary susceptibility caused by variants in the corresponding genes is low in Central European populations.
Clin Chem Lab Med 2009;47:398–404.
Keywords: alcoholic; genetic; interleukin-1β; liver cirrhosis; polymorphism; tumor necrosis factor-α
Received: 2008-11-21
Accepted: 2009-1-20
Published Online: 2009-03-12
Published in Print: 2009-04-01
©2009 by Walter de Gruyter Berlin New York
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Schlagwörter für diesen Artikel
alcoholic;
genetic;
interleukin-1β;
liver cirrhosis;
polymorphism;
tumor necrosis factor-α
Artikel in diesem Heft
- Minireview
- Risk loci for type 2 diabetes – Quo vadis?
- Genetics and Molecular Diagnostics
- A common variant in the FTO gene is associated with body mass index in males and postmenopausal females but not in premenopausal females. Czech post-MONICA and 3PMFs studies
- Genotype distribution of estrogen receptor α polymorphisms in pregnant women from healthy and preeclampsia populations and its relation to blood pressure levels
- Do common genetic variants in endotoxin signaling pathway contribute to predisposition to alcoholic liver cirrhosis?
- The selection and application of ssDNA aptamers against MPT64 protein in Mycobacterium tuberculosis
- Stromal cell-derived factor-1 but not its receptor, CXCR4, gene variants increase susceptibility and pathological development of hepatocellular carcinoma
- Expression of lineage markers using real-time quantitative polymerase chain reaction (RT-qPCR) in normal and in leukemia bone marrow
- Translation termination and protein folding pathway genes are not correlated in gastric cancer
- General Clincial Chemistry and Laboratory Medicine
- Novel serum paraoxonase activity assays are associated with coronary artery disease
- Elevated erythrocyte carbonic anhydrase activity is a novel clinical marker in hyperventilation syndrome
- Elevation of the glycoxidation product Nε-(carboxymethyl)lysine in patients presenting with acute myocardial infarction
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- A high-performance liquid chromatography method for the determination of carbamazepine and carbamazepine-10,11-epoxide and its comparison with chemiluminescent immunoassay
- Reference Values and Biological Variations
- Minimizing the effects of multicollinearity in the polynomial regression of age relationships and sex differences in serum levels of pregnenolone sulfate in healthy subjects
- Determination of physiological plasma pentraxin 3 (PTX3) levels in healthy populations
- Validation and Outcome Studies
- Analytical precision of the Urolizer® for the determination of the BONN-Risk-Index (BRI) for calcium oxalate urolithiasis and evaluation of the influence of 24-h urine storage at moderate temperatures on BRI
- Determination of nitrotyrosine concentrations in plasma samples of diabetes mellitus patients by four different immunoassays leads to contradictive results and disqualifies the majority of the tests
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